Life Science Journal 2013;10(4) http://www.lifesciencesite.com http://www.lifesciencesite.com lifesciencej@gmail.com 327 Monoamine Oxidase A and B Inhibitors of Some Synthesized Heterocyclic Derivatives and Their Structure Activity Relationships Mohamed M. Abdulla 1 , Mohamed A. Al-Omar 2 and Abd El-Galil E. Amr 2,3, * 1 Research Unit, Saco Pharm. Co., 6 th October City 11632, Egypt 2 Pharmaceutical Chemistry Department, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia 3 Applied Organic Chemistry Department, National Research Center, Dokki, Cairo, Egypt. * aeamr1963@yahoo.com Abstract: We herein report the monoamine oxidases A and B inhibitors of some synthesized substituted pyrimidines, thiazolopyrimidines and pyrazoles derivatives. Seventeen pyrimidine, thiazolo-pyrimidine, pyrazole, and pyridine derivatives 1-17 containing a carboxamide, ester, amide and ketone groups attached to a heterocyclic moiety synthesized and screened for their monoamine oxidases A and B inhibitors activities. The newly synthesized derivatives containing pyrimidine, thiazolopyrimidine, pyrazole, and pyridine moieties linked with different function groups considered as a lead for potent monoamine oxidases A and B inhibitors agents. The detailed synthetic pathways of obtained compounds and monoamine oxidases A and B inhibitors were reported. [Mohamed M. Abdulla, Mohamed A. Al-Omar and Abd El-Galil E. Amr. Monoamine Oxidase A and B Inhibitors of Some Synthesized Heterocyclic Derivatives and Their Structure Activity Relationships. Life Sci J 2013; 10(4):327-335] (ISSN: 1097-8135). http://www.lifesciencesite.com . 43 Keywords: 5-Chloroanisic acid; Pyrimidines; Thiazolopyrimidine; monoamine oxidases A and B inhibitors; SAR. 1. Introduction In our previous work, we reported that certain substituted pyridines and their chiral macrocyclic derivatives have anticancer, antimicrobial, analgesic, anti-inflammatory and anticonvulsant activities (Al- Mohizea et al., 2012; Al-Harbi et al., 2013; Amr et al., 2006, 2005; Bahashwan et al., 2012; Abo-Ghalia and Amr, 2004 and Hammam et al., 2003). Some substituted heterocyclic derivatives showed anti- inflammatory (Al-Omar et al., 2010; Xu et al., 2001) and anticancer agents (Bailly et al., 1999; van Hattum et al., 2002; He et al., 2003) and also showed analgesic activities (Abdel Salam et al., 2013; Yang et al., 2002; Min et al., 2003). Recently, some new substituted pyridine, and pyrazolopyrimidine derivatives has been synthesized and showed potent analgesic, anticonvulsant, anti-parkinsonism, hypoglycemic and anti-microbial activities (Al-Harbi et al., 2013; Bahashwan et al., 2012; Abdel Salam et al., 2013; Alanazi et al., 2013). On the other hand, substituted heterocyclic derivatives showed different promising biological activities (Attia et al., 1995, 1997, 2000). Monoamine oxidases (MAOs) are FAD depending enzymes responsible for the regulation and metabolism of major monoamine neurotransmitters [5-hydroxytryptamine (5-HT), norepinephrine (NE), and dopamine (DA)], modulating their concentrations in the brain and peripheral tissues (Shih, et al., 1999). They are also involved in the biodegradation of exogenous amines such as 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) into 1-methyl-4-phenyl pyridinium (MPP+), a Parkinson producing neurotoxin (Chiba, et al., 1984; Fritz, et al., 1985; Grimsby, et al., 1997). The MAO enzyme exists in two forms, namely MAO-A and MAO-B, distinguishable by their molecular cloning, substrate and inhibitor selectivity, and tissue distribution (Bach et al., 1988; Johnston et al., 1968; Kalgutka et al., 1995; Westlund et al., 1985). MAO-A preferentially oxidizes serotonin and is irreversibly inhibited by low concentrations of clorgyline, while that of the B isoform preferentially oxidizes β-phenylethylamine (PEA) and benzylamine and it is irreversibly inactivated by low concentrations of L-deprenyl (Knoll et al., 1972). Dopamine, tyramine, and tryptamine are common substrates for both MAOs. In fact, human MAO-A inhibitors are antidepressants and antianxiety agents (Rudorfer, et al., 1989), while human MAO-B inhibitors are used alone or in combination with other drugs in the therapy of Alzheimer’s and Parkinson’s diseases (Gerlach et al., 2003; Riederer et al., 2004). In view of these reports and as a continuation of our previous works in fused poly-heterocyclic ring systems, herein we screened some of newly synthesized substituted thioxopyrimidine, and thiazolopyrimidine for the their monoamine oxidases A and B inhibiting activities. 2. Experimental Chemistry All melting points were taken on Electrothermal IA 9000 series digital melting point apparatus. Elemental analytical data (in accord with the